1. Field of the Invention
The present invention relates to apparatus and methods for the measurement of physiological functions, and, more particularly, to noninvasive apparatus and methods for the measurement of cardiac valve function.
2. Description of Related Art
Background on Cardiovascular Function Assessment Techniques
The cardiac cycle in a human heart is a well-studied phenomenon. As shown in FIG. 1 (Guyton, Basic Human Physiology, W.B. Saunders Co., Philadelphia, Pa., 1971), pressure, volumetric, electrical, and audible events can be correlated with the stages of the cardiac cycle.
Electrocardiograms (EKGs) detect the electrical potentials generated in the heart, but their interpretation is largely empirical, as the phenomena the peaks represent are not wholly understood, and diagnoses are primarily made via pattern matching techniques against known normal and disease states. Some myopathies that can be detected with an EKG are ventricular hypertrophy, bundle branch blocks, and fibrillation. However, such problems as valvular stenosis and regurgitation cannot be detected with an EKG, nor can transvalvular pressure gradients be assessed.
Cardiac catheterization is a technique that is used to measure blood pressure in various areas of the heart, as well as blood pumping rate and blood chemistry analysis. This procedure, however, has a nontrivial risk associated with it, even in relatively healthy patients, and infants and heart transplant patients are typically not candidates.
Echocardiographic techniques, including Doppler echocardiography, utilizes returned ultrasound pulses to map a graphic image of the heart and blood vessels, yielding information on the size, shape, and motion of the heart chambers and great vessels and the motion of the heart valves. It has recently been found that this method can compare favorably with cardiac catheterization in making assessments of cardiac hemodynamics in patients with cardiac disease (Dobaghi et al., Am. J. Cardiol. 76, 392, 1995; Nishimura and Tajik, Prog. Cardiovasc. Dis. 36, 309, 1994).
Esophageal echocardiography, in which a tube is placed down the patient's throat for visualizing the back of the heart, can detect a valve leakage, but this technique is expensive and uncomfortable, and requires great expertise to administer.
Heart sounds, which have been monitored in a gross manner via auscultation for hundreds of years, are representative of the vibration of the walls of the heart and major vessels around the heart caused by closure of the valves. The phonocardiogram is a recording of amplified low-frequency heart sounds detected by a microphone placed on the patient's chest. Abnormalities such as mitral and aortic stenosis, mitral and aortic regurgitation, and patent ductus arteriosus can be detected with this noninvasive technique.
Value Area Assessment Techniques
As early as the 1930s methods for obtaining sufficient hemodynamic information for the assessment of valvular stenosis through the application of hydraulic principles were becoming routinely available. However, it was not until 1951 that Gorlin and Gorlin published an orifice formula based upon hydraulic principles using information derived from cardiac catheterization.
The work of Gorlin and Gorlin represented a major advance in the diagnosis of stenotic valvular cardiac disease through the ability to reproducibly quantify the degree of stenosis in terms of valvular area. While this method has become almost universally accepted as the standard for assessing valvular stenosis, it does subject the patient to the highly invasive procedure of cardiac catheterization. It would be rewarding both from the point of view of improved patient care and evaluation and in the further understanding of cardiac mechanics if a method were developed that used diagnostic parameters of a less invasive nature than is the current practice.
The principal hemodynamic manifestations of a significant degree of aortic stenosis include an increased left ventricular pressure, "a" waves in the left atrial pressure pulse, an abnormally large systolic aortic valve pressure gradient whose value depends on the forward systolic flow rate, central aortic pressure pulse abnormalities, a prolonged systolic ejection interval and reduced cardiac output and coronary blood flow.
All these measurable manifestations of aortic stenosis are related to the degree of valvular stenosis but do not, in themselves, provide a quantification of the magnitude of the obstruction. Alterations in the fundamental hemodynamic variables of stroke volume, aortic valve pressure gradient and left ventricular ejection period are the basis for interpreting the principle clinical manifestations of aortic stenosis.
The hemodynamic foundation for the quantification of aortic stenosis from the fundamental variables was established by the investigations of Gorlin and Gorlin (1951). The principal result of these studies was the development of a hydraulic orifice formula that derived from a combination of two basic laws of fluid physics, the conservation of energy and conservation of mass. The resulting orifice formula determined the degree of outflow obstruction as specified by the aortic valve cross-sectional area. The valve area is precisely related to stroke volume, aortic valve pressure gradient, and systolic ejection time. Since the introduction of this hydraulic formula, it has become the most generally accepted diagnostic procedure for the accurate quantification of the degree of obstruction associated with aortic stenosis.
Despite the fundamental character of a diagnosis via the Gorlin formula, the highly invasive nature of the required hemodynamic measurements often necessitates diagnostic procedures of a less precise nature. Thus it would be desirable to provide a technique that would provide more precise data while at the same time presenting no risk to the patient.
Valve Pressure Gradient Assessment Techniques
Mitral valve disease is the result of a reaction on cardiac valve tissue of the body's defense mechanisms against a particular form of streptococcal infection known as rheumatic fever.
As a result of the relatively good public health measures in the industrialized world, mitral valve disease no longer represents the critical proportions that it assumes in the undeveloped world. Nevertheless, this disease still accounts for a significant health care concern. Statistics of the American Heart Association for 1978 indicate that approximately nine million adults have rheumatic heart disease in the United States, and the death rate due to this affliction is about 13,000 per year. Over one-half of all patients with rheumatic heart disease also develop mitral stenosis, and of this number 66% are women.
Of particular concern is heart disease in pregnancy. Heart disease of all classes occurs in approximately 1% of women of child-bearing age; however, rheumatic heart disease, particularly mitral stenosis, accounts for 90-95% of heart disease observed during pregnancy. Prenatal mortality rates are also strongly dependent on the degree of mitral stenosis. The infant mortality rate is approximately 12% for conditions of moderate maternal mitral stenosis and over 50% for severe mitral stenosis.
To minimize the maternal and fetal risks, it is recommended that pregnancies complicated by mitral stenosis be followed by serial observations of functional cardiac status. An important parameter of this abnormality is the capillary wedge pressure; however, it is clearly not feasible to perform serial catheterizations under these conditions.
Patients who have severe mitral valve disease are often given artificial valve replacements. While artificial valves alleviate the problem of stenosis, it is not uncommon for thrombi to form on the mechanical structures, producing systemic emboli and valve obstruction or re-stenosis. For this reason serial observation of the valve for possible malfunction and flow obstruction is important. Increased obstruction of the valve manifests itself by increased left atrial or capillary wedge pressure. A noninvasive estimate of pressure would be desirable to provide valuable diagnostic information for this class of patients.
Knowledge of the mitral valve area via the Gorlin and Gorlin method provides a quantitative measure of the severity of valve obstruction. Since the introduction of this method, the area computation has become a widely accepted diagnostic and investigative technique for cardiac valve obstructive disease. The fundamental variables required in the Gorlin formula are stroke volume, diastolic filling period (the duration that the valve is open), heart rate, and the pressure difference across the valve. Since cardiac echographic techniques now offer the possibility of determining stroke volume, heart rate, and diastolic filling period with good accuracy, it would be useful to have a method for estimating the pressure differential in an equally noninvasive manner. Doppler ultrasound will provide such a pressure estimate through application of the Bernoulli equation for the case of natural valves. The complex mechanical structure of many prosthetic valves precludes an accurate estimation of the blood jet velocity via Doppler methods, however.
It has proved possible to develop and verify an orifice equation that allows an expression of mitral valve area without explicit knowledge of the mitral valve gradient. This equation was validated using the original data of Gorlin and Gorlin and other published catheterization data. Furthermore, an effort to verify this equation using prospective echographic data has proved successful.
A significant method for assessment of the flow obstruction of aortic valves is to determine the pressure drop across the valve. The pressure drop across natural valves may be conveniently and noninvasively estimated by Doppler ultrasound velocity recordings with an approximate conversion to pressure via the Bernoulli equation. The more complex structure of prosthetic valves renders this technique less than meaningful. If stroke volume is known, an estimate of effective valve area may be obtained by the valve area formula.
Considerable effort has been directed to the assessment of left ventricular pressure, wall stress, and posterior wall thickness through ventricular dimension measurements. Furthermore, a relationship between aortic valve gradient and ventricular dimension has been suggested.
Current diagnostic techniques depend upon cardiac catheterization, Doppler ultrasound studies, or direct visualization of the mitral valve orifice by bi-dimensional echocardiography. It would thus be advantageous to provide a convenient and inexpensive screening test for natural and prosthetic mitral valve misfunction.
Assessment of Valvular Insufficiency
The pathogenesis of mitral and aortic regurgitation is extensive and varied. The conditions often present in association with, respectively, mitral/aortic stenosis or relative stenosis. While the etiology and symptoms are numerous, the one cardinal hemodynamic hallmark of this condition is a left ventricular stroke volume of greater magnitude than the forward stroke volume. This characteristic provides a basis for the quantitative assessment of the condition, through catheterization, angiography, or noninvasive methods. It would be useful to develop a noninvasive technique for estimating regurgitant fraction under conditions of pure or mixed mitral or aortic insufficiency.
Assessment of Stroke Volume
Numerous simplified mathematical formulations for the estimation of stroke volume from elementary echographic measurements have been proposed. One investigation analyzed eight recently proposed echographic formulae for stroke volume by comparing Fick principle and thermodilution determinations of cardiac output with M-mode echocardiographically derived values by simultaneous measurement of the appropriate echographic data. Comparison of the correlation coefficients for simultaneous stroke volume computations with values derived from cardiac catheterization has revealed that the Teichholz formula enjoyed the highest degree of correspondence with the invasive measurements and may be expected to correspond to invasive methods at a level of r=0.86 in the absence of wall motion asymmetries, hypokinesis, and arrhythmic states.
The cubic equation for cardiac volume represents the ventricular volume at any phase of the cardiac cycle in terms of a constant fraction (.pi./3) of the volume of a sphere. Teichholz et al. proposed an alternative model based upon the recognition that the ratio of the principal dimension of the ventricle does not remain constant from systole to diastole. This investigation analyzed the ventricular dimension in systole and diastole for 100 left ventricular configurations and permitted the derivation of a correction factor to the cubic equation that, on the average, accounted for the change in width-to-length ratio of the heart during contraction. Ventricular volume by this formula is represented by a single cardiac dimension measured perpendicular to the long axis of the heart at the level of the mitral valve. According to this model, cardiac volume is given as V=7D.sup.3 /(2.4+D), where V is the cardiac volume in milliliters for any particular value of the ventricular dimension D measured in centimeters. The term 7/(2.4+D) may be viewed as a correction factor to the cubic formula, V=D.sup.3, accounting for the changing D/L ratio during ventricular contraction, L being the apex-to-base length.